The lpr gene is a single autosomal recessive gene which is responsible for the massive lymphoproliferation and autoimmunity in the MRL/lpr mouse. This gene has been transferred into three normal mouse strains. We propose to study the development of autoimmunity in these lpr congeneic mice. Further we will investigate the important interaction between antigen presenting macrophages and T-cells in the setting of spontaneous autoimmunity. We will study the ability of lpr derived cells to interact with normal congeneic cells to produce T-cell proliferation and interleukin-2. The modulating effects of in vivo treatment with sex hormones and interleukin-2 upon these cellular interactions will be studied.